Ecto-5′-Nucleotidase and Cardioprotection
When brief periods of ischemia precede sustained ischemia, infarct size is markedly limited, a phenomenon known as ischemic preconditioning. The main target for the recent basic research on ischemic preconditioning is to seek how adenosine relates to the infarct size-limiting effect. One possibility is that ischemic preconditioning augments release of adenosine during ischemia and reperfusion. To test this idea, we examined whether ischemic preconditioning activates the enzyme responsible for adenosine release, i.e., 5′-nucleotidase, and tested the cause-effect relationship between activation of 5′-nucleotidase and the infarct size-limiting effect. We found that activation of ecto-5′-nucleotidase plays a crucial role for attenuation of infarct size. Ischemic preconditioning increased ecto-5′-nucleotidase activity and adenosine release during reperfusion. An inhibitor of ecto-5′-nucleotidase blunted the infarct size-limiting effect of ischemic preconditioning. Furthermore, activation of ecto-5′-nucleotidase was attributable to the activation of protein kinase C via α1-adrenoceptor stimulation, because both prazosin and GF109203X (an inhibitor of protein kinase C) blunted the activation of ecto-5′-nucleotidase and thereby attenuated the infarct size-limiting effect. We found the phosphorylation of eeto-5′-nucleotidase due to activation of protein kinase C either by the treatment with phorbol ester or by ischemic preconditioning, suggesting that phosphorylation of this enzyme due to protein kinase C may play a key role for activation of ecto-5′-nucleotidase. We also found that transfection of ecto-5′-nucleotidase in the rat neonatal cardiomyocytes exerts potent cytoprotection against hypoxia and reoxygenation injury. Taken together, we propose potential mechanisms for cardioprotection attributable to activation of ecto-5′-nucleotidase in ischemic preconditioning.
KeywordsInfarct Size Ischemic Precondition Coronary Occlusion Nucleotidase Activity Adenosine Concentration
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